Caracterización de la vía de señalización intracelular mediada por IGF2R en trofoblasto humano

ilustraciones, fotografías, gráficas

Autores:
Castro Badilla, Juan José
Tipo de recurso:
Doctoral thesis
Fecha de publicación:
2021
Institución:
Universidad Nacional de Colombia
Repositorio:
Universidad Nacional de Colombia
Idioma:
spa
OAI Identifier:
oai:repositorio.unal.edu.co:unal/80608
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/80608
https://repositorio.unal.edu.co/
Palabra clave:
570 - Biología
Receptor IGF Tipo 2
Receptor IGF Tipo 1
Proteínas Tirosina Quinasas Receptoras
Receptor, IGF Type 2
Receptor, IGF Type 1
Receptor Protein-Tyrosine Kinases
IGF receptor
HTR-8/SVneo
Factor de crecimiento similar a insulina tipo 2
Implantación
Placenta
Obesidad
IGF receptor
Insulin-like growth factor type 2
Implantation
Obesity
Rights
openAccess
License
Atribución-SinDerivadas 4.0 Internacional
id UNACIONAL2_08c41a651be3f9e8960a8e42021ee006
oai_identifier_str oai:repositorio.unal.edu.co:unal/80608
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv Caracterización de la vía de señalización intracelular mediada por IGF2R en trofoblasto humano
dc.title.translated.eng.fl_str_mv Characterization of the intracellular signaling mediated by IGF2R in human trophoblast
title Caracterización de la vía de señalización intracelular mediada por IGF2R en trofoblasto humano
spellingShingle Caracterización de la vía de señalización intracelular mediada por IGF2R en trofoblasto humano
570 - Biología
Receptor IGF Tipo 2
Receptor IGF Tipo 1
Proteínas Tirosina Quinasas Receptoras
Receptor, IGF Type 2
Receptor, IGF Type 1
Receptor Protein-Tyrosine Kinases
IGF receptor
HTR-8/SVneo
Factor de crecimiento similar a insulina tipo 2
Implantación
Placenta
Obesidad
IGF receptor
Insulin-like growth factor type 2
Implantation
Obesity
title_short Caracterización de la vía de señalización intracelular mediada por IGF2R en trofoblasto humano
title_full Caracterización de la vía de señalización intracelular mediada por IGF2R en trofoblasto humano
title_fullStr Caracterización de la vía de señalización intracelular mediada por IGF2R en trofoblasto humano
title_full_unstemmed Caracterización de la vía de señalización intracelular mediada por IGF2R en trofoblasto humano
title_sort Caracterización de la vía de señalización intracelular mediada por IGF2R en trofoblasto humano
dc.creator.fl_str_mv Castro Badilla, Juan José
dc.contributor.advisor.spa.fl_str_mv Umaña Pérez, Yadi Adriana
dc.contributor.author.spa.fl_str_mv Castro Badilla, Juan José
dc.contributor.researchgroup.spa.fl_str_mv Grupo de Investigación en Hormonas
dc.subject.ddc.spa.fl_str_mv 570 - Biología
topic 570 - Biología
Receptor IGF Tipo 2
Receptor IGF Tipo 1
Proteínas Tirosina Quinasas Receptoras
Receptor, IGF Type 2
Receptor, IGF Type 1
Receptor Protein-Tyrosine Kinases
IGF receptor
HTR-8/SVneo
Factor de crecimiento similar a insulina tipo 2
Implantación
Placenta
Obesidad
IGF receptor
Insulin-like growth factor type 2
Implantation
Obesity
dc.subject.decs.spa.fl_str_mv Receptor IGF Tipo 2
Receptor IGF Tipo 1
Proteínas Tirosina Quinasas Receptoras
dc.subject.decs.eng.fl_str_mv Receptor, IGF Type 2
Receptor, IGF Type 1
Receptor Protein-Tyrosine Kinases
dc.subject.proposal.spa.fl_str_mv IGF receptor
HTR-8/SVneo
Factor de crecimiento similar a insulina tipo 2
Implantación
Placenta
Obesidad
dc.subject.proposal.eng.fl_str_mv IGF receptor
Insulin-like growth factor type 2
Implantation
Obesity
description ilustraciones, fotografías, gráficas
publishDate 2021
dc.date.accessioned.none.fl_str_mv 2021-10-25T15:27:11Z
dc.date.available.none.fl_str_mv 2021-10-25T15:27:11Z
dc.date.issued.none.fl_str_mv 2021-04-23
dc.type.spa.fl_str_mv Trabajo de grado - Doctorado
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/doctoralThesis
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/acceptedVersion
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_db06
dc.type.content.spa.fl_str_mv Text
dc.type.redcol.spa.fl_str_mv http://purl.org/redcol/resource_type/TD
format http://purl.org/coar/resource_type/c_db06
status_str acceptedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unal.edu.co/handle/unal/80608
dc.identifier.instname.spa.fl_str_mv Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv https://repositorio.unal.edu.co/
url https://repositorio.unal.edu.co/handle/unal/80608
https://repositorio.unal.edu.co/
identifier_str_mv Universidad Nacional de Colombia
Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv spa
language spa
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dc.publisher.spa.fl_str_mv Universidad Nacional de Colombia
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dc.publisher.branch.spa.fl_str_mv Universidad Nacional de Colombia - Sede Bogotá
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spelling Atribución-SinDerivadas 4.0 Internacionalhttp://creativecommons.org/licenses/by-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Umaña Pérez, Yadi Adrianad652013090d46425f836051252c18e62Castro Badilla, Juan José4fe46cf9c7b4b4d5df2b84249719f715Grupo de Investigación en Hormonas2021-10-25T15:27:11Z2021-10-25T15:27:11Z2021-04-23https://repositorio.unal.edu.co/handle/unal/80608Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, fotografías, gráficasEl factor de crecimiento similar a la insulina tipo 2, IGF2, ejerce acciones a través de los receptores de la familia IGF incluyendo el receptor tipo 1 (IGF1R), el receptor de insulina (IR) y los híbridos IGF1R/IR. Preferentemente, su acción es mediada a través del receptor IGF1R modulando rutas de señalización intracelulares esenciales en procesos como la proliferación, migración o invasión celular, eventos que son de carácter crucial en las manifestaciones patológicas originadas en el trofoblasto, tales como la enfermedad trofoblástica gestacional, molas, preeclampsia o la restricción de crecimiento intrauterino, siendo estas complicaciones un problema actual para la salud pública del país. Se ha descrito que en tejido de mola la expresión de IGF2 se encuentra elevada y, además, que participa activamente en el proceso de la embriogénesis. La regulación de la biodisponibilidad de este ligando se atribuye, entre otros, a la unión con el receptor IGF2R, el cual lo internaliza para su degradación. Sin embargo, hace más de una década existe controversia sobre si esta interacción lGF2/IGF2R puede desencadenar una vía de señalización que participe en los procesos celulares descritos anteriormente. En este orden de ideas, para explorar si existe una vía de señalización dependiente de IGF2R, sin la activación directa de los otros receptores de la familia, se usó como estrategia estimular células derivadas de trofoblasto humano HTR-8/SVneo con Leu27IGF2, péptido análogo de IGF2, que se une exclusivamente al IGF2R. La inducción de las células con el análogo generó una activación temprana de las proteínas ERK1 y 2 mayor a la inducida por el IGF2. Se observó un incremento en los niveles de transcripción de MMP-9 de carácter tiempo-dependiente de Leu27IGF2 y anticipado con respecto al péptido IGF2, concordante con un aumento temprano de la actividad gelatinasa de MMP-9. Se determinó que la interacción de IGF2R con Leu27IGF2 generó un incremento significativo del 20%, 13% y 23% en adhesión, migración y proliferación celular respectivamente. Resultados que nos sugieren que el IGF2 en células de trofoblasto, activa al receptor IGF2R y al menos una ruta de señalización, como la de MAPKs, involucrada en el aumento de la activación de proteínas y transcripción de genes que favorecen la adhesión, migración e invasión celular durante la implantación blastocística. (Texto tomado de la fuente).The insulin-like growth fact or type 2, IGF2, exerts actions through receptors in the IGF family including the type 1 receptor (IGF1R), the insulin receptor (IR) and IGF1R/IR hybrids. Preferably, its action is mediated through the IGF1R receptor modulating intracellular signaling pathways essential in processes such as cell proliferation, migration or invasion, events that are crucial in the pathological manifestations originated by the trophoblast, such as gestational trophoblastic diseases, moles, preeclampsia or intrauterine growth restriction, being these complications a current problem for the public health of the country. It has been described that the expression of IGF2 in mole tissue is high and, in addition, that it actively participates in the embryogenesis process. The regulation of the bioavailability of this ligand is attributed, among others, to the binding with the IGF2R receptor which internalizes it for degradation. However, for more than a decade there has been controversy about whether this interaction lGF2/IGF2R can trigger a signaling pathway involved in the cellular processes described above. In this order of ideas to explore if there is an IGF2R-dependent signaling pathway, without the direct activation of the other receptors of the family, a strategy was used to stimulate cells derived from human trophoblast HTR-8/SVneo with Leu27IGF2, an analogous peptide of IGF2, which binds exclusively to IGF2R. The induction of cells with the analogue generated a higher early activation of ERK1 and 2 proteins compared to that induced by IGF2. Similarly, an increase in the transcription levels of Leu27IGF2-dependent and anticipated MMP-9 with respect to IGF2 peptide was observed, consistent with an early increase in MMP-9 gelatinase activity. It was determined that interaction of IGF2R with Leu27IGF2 generated a significant increase of approximately 20%, 13% and 23% in adhesion, migration and cell proliferation respectively with respect to basal condition. These results suggest that IGF2 in trophoblast cells activates the IGF2R receptor and at least one signaling pathway, such as MAPKs, involved in increased protein activation and gene transcription that favor cell adhesion, migration and invasion during blastocyst implantation.DoctoradoDoctor en Ciencias - BioquímicaFactores de crecimiento, diferenciación y cáncerDepartamento de Químicaxvii, 74 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Doctorado en Ciencias - BioquímicaDepartamento de QuímicaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá570 - BiologíaReceptor IGF Tipo 2Receptor IGF Tipo 1Proteínas Tirosina Quinasas ReceptorasReceptor, IGF Type 2Receptor, IGF Type 1Receptor Protein-Tyrosine KinasesIGF receptorHTR-8/SVneoFactor de crecimiento similar a insulina tipo 2ImplantaciónPlacentaObesidadIGF receptorInsulin-like growth factor type 2ImplantationObesityCaracterización de la vía de señalización intracelular mediada por IGF2R en trofoblasto humanoCharacterization of the intracellular signaling mediated by IGF2R in human trophoblastTrabajo de grado - Doctoradoinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_db06Texthttp://purl.org/redcol/resource_type/TD1. 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Proc Natl Acad Sci. 1993;90: 10305. doi:10.1073/pnas.90.21.10305“Caracterización de la vía de señalización intracelular mediada por IGF-IIR en trofoblasto humano”, código Hermes 39172InvestigadoresPúblico generalLICENSElicense.txtlicense.txttext/plain; charset=utf-83964https://repositorio.unal.edu.co/bitstream/unal/80608/1/license.txtcccfe52f796b7c63423298c2d3365fc6MD51ORIGINAL528066.2020.pdf528066.2020.pdfTesis de Doctorado en Ciencias - Bioquímicaapplication/pdf2353128https://repositorio.unal.edu.co/bitstream/unal/80608/2/528066.2020.pdf864d2859ddc7f729cc56f13cf4bc212bMD52THUMBNAIL528066.2020.pdf.jpg528066.2020.pdf.jpgGenerated Thumbnailimage/jpeg5366https://repositorio.unal.edu.co/bitstream/unal/80608/3/528066.2020.pdf.jpgb1a1c21cbf0687c7b1ea2c392b730b53MD53unal/80608oai:repositorio.unal.edu.co:unal/806082024-07-31 23:13:58.617Repositorio Institucional Universidad Nacional de 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GVyZWNob3MgZGUgYXV0b3IgcXVlIGNvbmxsZXZlIGxhIGRpc3RyaWJ1Y2nDs24gZGUgZXN0b3MgYXJjaGl2b3MgeSBtZXRhZGF0b3MuCkFsIGhhY2VyIGNsaWMgZW4gZWwgc2lndWllbnRlIGJvdMOzbiwgdXN0ZWQgaW5kaWNhIHF1ZSBlc3TDoSBkZSBhY3VlcmRvIGNvbiBlc3RvcyB0w6lybWlub3MuCgpVTklWRVJTSURBRCBOQUNJT05BTCBERSBDT0xPTUJJQSAtIMOabHRpbWEgbW9kaWZpY2FjacOzbiAyNy8yMC8yMDIwCg==

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